دورية أكاديمية
The role of C5aR1-mediated hepatic macrophage efferocytosis in NASH.
| العنوان: | The role of C5aR1-mediated hepatic macrophage efferocytosis in NASH. |
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| المؤلفون: | Shen X; Department of Basic Medicine, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, China.; Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, Jiamusi, 154000, Heilongjiang, China., Zheng W; Department of Endocrinology, The First Huaian Hospital Affiliated to Nanjing Medical University, Huai'an, 223300, Jiangsu, China., Du X; Department of Basic Medicine, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, China., Chen Y; Department of Basic Medicine, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, China., Song X; Department of Basic Medicine, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, China., Yang L; Department of Basic Medicine, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, China. jsyc.ylc@163.com., Yuan Q; Department of Endocrinology, The First Huaian Hospital Affiliated to Nanjing Medical University, Huai'an, 223300, Jiangsu, China. yuanqi_1991@163.com. |
| المصدر: | Scientific reports [Sci Rep] 2024 Jul 26; Vol. 14 (1), pp. 17232. Date of Electronic Publication: 2024 Jul 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
| مواضيع طبية MeSH: | Non-alcoholic Fatty Liver Disease*/metabolism , Non-alcoholic Fatty Liver Disease*/pathology , Receptor, Anaphylatoxin C5a*/metabolism , Receptor, Anaphylatoxin C5a*/genetics , Macrophages*/metabolism , Liver*/metabolism , Liver*/pathology , NLR Family, Pyrin Domain-Containing 3 Protein*/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein*/genetics , Phagocytosis*, Animals ; Mice ; Humans ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Apoptosis ; Alanine Transaminase/blood ; Alanine Transaminase/metabolism ; Aspartate Aminotransferases/blood ; Aspartate Aminotransferases/metabolism ; Efferocytosis |
| مستخلص: | Non-alcoholic fatty liver disease (NAFLD) has become the first major chronic liver disease in developed countries. 10-20% of NAFLD patients will progress to non-alcoholic steatohepatitis (NASH), and up to 25% of NASH patients may develop cirrhosis within 10 years. Therefore, it is critical to find key targets that may treat this disease. Here, we identified C5aR1 as a highly-expressed gene in NASH mouse model through analyzing Gene Expression Omnibus (GEO) database and confirmed its higher expression in livers of NASH patients than that of NAFL patients. Meanwhile, we verified its positive correlation with patients' serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In vivo and in vitro experiments revealed that knocking down C5aR1 in liver significantly reduced liver weight ratio and serum ALT and AST levels and attenuated inflammatory cell infiltration and cell apoptosis in the liver of NASH mice as well as enhanced the efferocytotic ability of liver macrophages, suggesting that C5aR1 may play a crucial role in the efferocytosis of liver macrophages. Furthermore, we also found that the expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1β and other inflammation-related factors in the liver were significantly reduced. Our work demonstrates a potential mechanism of how C5aR1 deficiency protects against diet-induced NASH by coordinating the regulation of inflammatory factors and affecting hepatic macrophage efferocytosis. (© 2024. The Author(s).) |
| References: | J Hepatol. 2022 Jun;76(6):1263-1278. (PMID: 35589249) Sci Immunol. 2021 Dec 24;6(66):eabf2489. (PMID: 34932384) Trends Pharmacol Sci. 2022 Aug;43(8):653-668. (PMID: 35513901) Metabolism. 2016 Aug;65(8):1038-48. (PMID: 26823198) Cell Metab. 2021 Oct 5;33(10):2004-2020.e9. (PMID: 34614409) Nature. 2020 Dec;588(7836):146-150. (PMID: 32726800) Cell Mol Immunol. 2021 Aug;18(8):2059-2060. (PMID: 33976405) Front Immunol. 2021 Apr 15;12:652242. (PMID: 33936074) Cell Metab. 2021 Dec 7;33(12):2445-2463.e8. (PMID: 34784501) Immunity. 2023 Jan 10;56(1):58-77.e11. (PMID: 36521495) Mol Aspects Med. 2020 Dec;76:100889. (PMID: 32859386) Nat Rev Immunol. 2020 Apr;20(4):254-267. (PMID: 31822793) Cytokine Growth Factor Rev. 2021 Dec;62:42-53. (PMID: 34742632) Theranostics. 2020 Aug 1;10(21):9702-9720. (PMID: 32863955) Hepatology. 2023 Apr 1;77(4):1335-1347. (PMID: 36626630) Cell Rep. 2021 Jan 12;34(2):108626. (PMID: 33440159) Acta Paediatr. 2018 Feb;107(2):322-327. (PMID: 28981167) Gastroenterology. 2021 Sep;161(3):1030-1042.e8. (PMID: 34416976) Mol Immunol. 2016 Jul;75:122-32. (PMID: 27280845) Hepatology. 2016 Jul;64(1):73-84. (PMID: 26707365) Nat Rev Gastroenterol Hepatol. 2018 Jan;15(1):11-20. (PMID: 28930295) Theranostics. 2020 Jul 9;10(19):8619-8632. (PMID: 32754267) Viruses. 2019 Jan 09;11(1):. (PMID: 30634407) Cancer Cell. 2018 Oct 8;34(4):561-578.e6. (PMID: 30300579) Immunity. 2022 Sep 13;55(9):1515-1529. (PMID: 36103850) J Hepatol. 2022 Aug;77(2):312-325. (PMID: 35292349) J Hepatol. 2022 May;76(5):1001-1012. (PMID: 34942286) Int J Mol Sci. 2021 May 31;22(11):. (PMID: 34072916) Science. 2016 Jun 17;352(6292):aad1210. (PMID: 27313051) World J Gastroenterol. 2010 Nov 14;16(42):5286-96. (PMID: 21072891) Signal Transduct Target Ther. 2022 Aug 13;7(1):287. (PMID: 35963848) Nat Med. 2018 Jul;24(7):908-922. (PMID: 29967350) Gastroenterology. 2014 Oct;147(4):765-783.e4. (PMID: 25046161) Lancet. 2021 Jun 5;397(10290):2212-2224. (PMID: 33894145) Front Cell Dev Biol. 2022 Feb 25;10:839248. (PMID: 35281078) Am J Gastroenterol. 2019 Oct;114(10):1626-1635. (PMID: 31517638) |
| معلومات مُعتمدة: | H2023069 Medical Research Project of Jiangsu Health and Health Commission; YK2023027 Medical Research Project of Yancheng Health and Health Commission; Z-2017-26-2202-4 China International Medical Exchange Foundation Medical road Hengrui Diabetes metabolism Research Fund; HAB202302 Huaian City natural science research project |
| فهرسة مساهمة: | Keywords: C5aR1; Efferocytosis; Inflammatory factors; Macrophage; NASH |
| المشرفين على المادة: | 0 (Receptor, Anaphylatoxin C5a) 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0 (C5ar1 protein, mouse) 0 (C5AR1 protein, human) EC 2.6.1.2 (Alanine Transaminase) EC 2.6.1.1 (Aspartate Aminotransferases) |
| تواريخ الأحداث: | Date Created: 20240726 Date Completed: 20240727 Latest Revision: 20240806 |
| رمز التحديث: | 20240806 |
| مُعرف محوري في PubMed: | PMC11282180 |
| DOI: | 10.1038/s41598-024-68207-y |
| PMID: | 39060563 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2045-2322 |
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| DOI: | 10.1038/s41598-024-68207-y |